Leveraging Generative AI to Prioritize Drug Repurposing Candidates: Validating Identified Candidates for Alzheimer’s Disease in Real-World Clinical Datasets

Abstract

Abstract Drug repurposing represents an attractive alternative to the costly and time-consuming process of new drug development, particularly for serious, widespread conditions with limited effective treatments, such as Alzheimer’s disease (AD). Emerging generative artificial intelligence (GAI) technologies like ChatGPT offer the promise of expediting the review and summary of scientific knowledge. To examine the feasibility of using GAI for identifying drug repurposing candidates, we iteratively tasked ChatGPT with proposing the twenty most promising drugs for repurposing in AD, and tested the top ten for risk of incident AD in exposed and unexposed individuals over age 65 in two large clinical datasets: 1) Vanderbilt University Medical Center and 2) the All of Us Research Program. Among the candidates suggested by ChatGPT, metformin, simvastatin, and losartan were associated with lower AD risk in meta-analysis. These findings suggest GAI technologies can assimilate scientific insights from an extensive Internet-based search space, helping to prioritize drug repurposing candidates and facilitate the treatment of diseases.

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